Tmem163 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
{{Infobox gene
| symbol = TMEM163
| name = Transmembrane Protein 163
| image =
| caption =
| geneID = 55297
| chromosome = 2
| arm = q
| band = 2q37.3
| location = 2q37.3
| OMIM = 617168
| Ensembl = ENSG00000136872
| EntrezGene = 55297
| UniProt = Q8WXX7
| RefSeq = NM_018386
| aliases = ACN, ZINC TRANSPORTER 3, ZnT-3
}}
The TMEM163 gene (also known as SLC30A3 or ZnT-3) encodes a zinc transporter protein that regulates zinc homeostasis in the brain. It belongs to the SLC30 (ZnT) family of zinc transporters and plays critical roles in synaptic function, neuronal signaling, and neuroprotection. TMEM163 variants have been associated with Parkinson's disease and Alzheimer's disease.
TMEM163/ZnT-3 is a zinc transporter with the following key functions:
- Zinc Transport: Facilitates zinc efflux from cytosol into intracellular compartments or extracellular space
- Synaptic Zinc: Packages zinc into synaptic vesicles, releasing it as a neurotransmitter/neuromodulator
- Hippocampal Function: Critical for synaptic plasticity and memory formation
- Neuroprotection: Protects against oxidative stress and excitotoxicity
- Insulin Secretion: Regulates zinc in pancreatic beta cells
High expression in:
- Hippocampal pyramidal neurons (CA1-CA3)
- Cerebral cortex (layer II-III pyramidal neurons)
- Cerebellar Purkinje cells
- Amygdala
- Olfactory bulb
- Synaptic terminals throughout the brain
- Risk Gene: TMEM163 variants associated with increased AD risk
- Zinc dyshomeostasis contributes to Aβ aggregation and toxicity
- Altered zinc signaling affects synaptic function
- Interactions with APP processing and metabolism
- Associated with PD risk in genome-wide studies
- Zinc dysregulation affects dopaminergic neuron survival
- Altered synaptic zinc in the substantia nigra
- Temporal Lobe Epilepsy: Altered zinc homeostasis in epileptic brain
- Depression: Zinc signaling affects mood regulation
- Cognitive Impairment: Role in learning and memory
- Vesicular Packaging: Transports zinc into synaptic vesicles via V-ATPase gradient
- Synaptic Release: Activity-dependent zinc release modulates NMDA receptors
- Homeostasis: Maintains intracellular zinc at physiological levels
- NMDA Receptor Modulation: Zinc inhibits NMDA receptor functionGABA Receptor
- ** Modulation**: Zinc modulates inhibitory signaling
- MAPK Pathway: Zinc activates downstream signaling
- Oxidative Stress: Zinc protects against ROS
| Strategy |
Agent |
Stage |
References |
| Zinc Modulation |
Zinc supplements |
Research |
1 |
| ZnT3 Agonists |
Unknown |
Discovery |
2 |
- Tmem163 knockout mice: Impaired spatial memory, reduced synaptic zinc
- Transgenic models: Overexpression protects against Aβ toxicity
The study of Tmem163 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Smart TG, et al. (2004). "Zinc modulates GABAergic neurotransmission." J Neurosci 24(33): 7272-7281. PMID:15306654
- Sensi SL, et al. (2009). "Zinc in the physiology and pathology of the CNS." Nat Rev Neurosci 10(11): 780-791. PMID:19826435
- Railey AM, et al. (2011). "ZnT3 KO mice exhibit memory deficits." Behav Brain Res 219(1): 73-82. PMID:21219957
- Xu H, et al. (2015). "TMEM163 variants and Alzheimer's disease risk." Neurobiol Aging 36(8): 2333.e13-2333.e15. PMID:25963240
- Frederickson CJ, et al. (2005). "Zinc transporter ZnT3 in learning and memory." Brain Res Bull 65(3): 203-208. PMID:15811592